From Memory Key

Data from 789 men and 1,105 women from the Framingham Heart Study has found that those who had the lowest total cholesterol performed significantly more poorly on tests of similarities, word fluency, and attention/concentration than patients with higher cholesterol levels. Those in the lowest total cholesterol group (a level of under 200) were 49% more likely to perform poorly and 80% more likely to perform very poorly than were participants in the highest total cholesterol group (240 to 380). The finding should not be taken as a warning against those with high cholesterol taking medication to lower it; the study applies to those with naturally low cholesterol levels, and previous studies have shown that both high and low cholesterol have led to poor cognitive performance.

The study findings were published in the journal

Psychosomatic Medicine

From FoodNavigator-USA.com:

With all the focus on LDL (bad) cholesterol, a ‘virtually unknown’ form called oxycholesterol may pose the biggest heart health threat, say Chinese scientists.

Scientists from the Chinese University of Hong Kong identified fried and processed food as the main sources of oxycholesterol in the diet, statements that may lead to louder calls to reformulate towards ‘healthier’ foods.

“Total cholesterol, low-density lipoprotein cholesterol (LDL), and the heart-healthy high-density lipoprotein cholesterol (HDL) are still important health issues,” said lead researcher Zhen-Yu Chen, PhD.

“Our work demonstrated that oxycholesterol boosts total cholesterol levels and promotes atherosclerosis ["hardening of the arteries"] more than non-oxidized cholesterol.”

Sources

In an email communication with FoodNavigator, Dr Chen said: “Foods of animal origins contain cholesterol, which is stable at room temperature. However, it is susceptible to oxidation to produce the cholesterol oxidation products during heating, particularly, long frying and high temperature.

“The amount of cholesterol consumed from diet is about 300-500 mg cholesterol per day per person while cholesterol oxidation products could reach up to 10 per cent total cholesterol in diet.”

Oxycholesterol is produced in oxidised oils, particularly in the much-maligned trans-fatty acids and partially-hydrogenated vegetable oils. Health concerns, and the subsequent consumer reaction, have led many manufacturers to begin reformulating their products and reduce the trans-fat content, or eliminate it completely.

Detrimental effects of oxycholesterol have been on the researchers’ radars for a while, with the focus on cell and DNA damage, and its biochemical effects in contributing to atherosclerosis, said Dr Chen. According to the Hong Kong-based researchers, theirs is one of the first studies on oxycholesterol’s effects in raising blood cholesterol levels, compared to non-oxidized cholesterol.

Study details

According to findings presented at this week’s 238th National Meeting of the American Chemical Society, hamsters fed a diet high in oxycholesterol displayed blood cholesterol increases of up to 22 per cent more than hamsters eating non-oxidized cholesterol.

The oxycholesterol-fed group also showed greater deposition of cholesterol in the lining of their arteries and a tendency to develop larger deposits of cholesterol, called atherosclerotic plaques.

Diet vs pills

Chen noted that scientists do not know whether statins can lower oxycholesterol. “Statin is a type of drug which decreases cholesterol synthesis and thus decreases the cholesterol in blood,” he said. “Oxidized cholesterol is mainly from diet and statin should not have effect on oxidized cholesterol in blood but it needs to be proved.”

Consuming foods rich in antioxidants may be a way of countering these effects, said Chen said, since these substances may block the oxidation process that forms oxycholesterol.

There may a potential for dietary approaches said the researcher, such as phytosterols and phytostanols. “Phytosterols decreases blood cholesterol by a simple mechanism of decreasing cholesterol absorption,” said Chen. This could lead to greater excretion of oxycholesterol.

The study was funded by the Hong Kong Grant Research Council.

From MedicalNewsToday.com:

New research from two Philadelphia-area cardiologists finds that an over-the-counter dietary supplement sold at pharmacies and health food stores may be an alternative for patients who cannot take traditional statin medications to lower cholesterol because of statin-related muscle pain. The findings of their study, “Red Yeast Rice for Dyslipidemia in Statin-Intolerant Patients,” appear in the June 16, 2009 issue of Annals of Internal Medicine.

Cardiologists David Becker, M.D., and Ram Gordon, M.D., Chestnut Hill Cardiology, studied 62 patients with high cholesterol in the first randomized, double-blinded placebo-controlled trial to evaluate red yeast rice in patients with a history of statin-associated myalgias (side effects that include muscle pain and weakness). Thirty-one of the patients took three 600-mg capsules of red yeast rice twice per day over the course of six months, and the other half received identical placebo tablets. The red yeast rice patients also participated in weekly meetings for the first three months, where they were taught about heart disease and how to incorporate heart-healthy nutrition, exercise and stress management into their lives.

At the conclusion of the study, the research found:

- Low-density lipoprotein cholesterol (also known as “bad cholesterol”) levels decreased more in the patients receiving the red yeast rice (average decrease, 35 mg/dL) than in patients receiving the placebo (average decrease, 15 mg/dL).

- Total cholesterol levels improved more in the red yeast rice group than in the placebo group.

- Muscle pain scores, weight loss, HDL cholesterol (high-density lipoprotein or “good cholesterol”) and liver or muscle enzyme levels did not differ between the two groups.

Red Yeast Rice, a staple of Chinese medicine for more than a thousand years, is derived from a fungus that grows on rice. A series of compounds within the red yeast rice have been found to slow the production of cholesterol in the liver. The medical community, however, has been slow to consider its potential use as an alternative treatment therapy for patients with statin-associated myalgias because the supplement is not regulated by the Food and Drug Administration.

“Every physician has patients who refuse to take statins or have significant side effects from them,” says Dr. Becker. “One of the largest challenges in the medical community has been that there is no agreement or consensus on how to treat these patients. We are convinced that our research may lead to some answers.”

Dr. Gordon remarked, “Statins have revolutionized the way doctors have taken care of cardiac patients over the past two decades. But for patients that cannot tolerate them, the side effects are considerable.” Some studies have estimated that up to 15% of patients taking the cholesterol-lowering drugs have to stop because of muscle pain. According to IMS Health, a drug tracking company, more than 200 million statin prescriptions were filled in 2008.

Dr. Gordon added, “While red yeast rice isn’t appropriate for everyone, the goal of our research was to see if it has potential to be an option for those patients who discontinue their statins because of the side effects. Often these patients with high cholesterol are left without lipid-lowering therapy. This is especially worrisome if the patient has a history of heart attacks, stents, bypass surgery or strokes.”

Dr. Becker and Dr. Gordon are in private practice at Chestnut Hill Cardiology in Flourtown, Pennsylvania, a suburb of Philadelphia and are on the staff of Chestnut Hill Hospital and Abington Memorial Hospital. They also conduct an innovative cardiac prevention program called “Change of Heart,” which was developed by Dr. Becker in 1993. The 10-week program takes a holistic approach to cardiac wellness, utilizing diet, exercise, stress management and traditional and alternative treatment therapies to help people reduce and even reverse the effects of coronary artery disease.

Dr. Becker said, “Our present medical system places very little emphasis on educating patients. We employ a team approach. Patients work closely with dietitians, fitness experts and stress management counselors, and we provide the physician perspective to help them evaluate and consider traditional treatment and alternative therapies. We passionately believe that patients need to take control of their cardiac destiny.”

“Aside from its findings, this study is unique because it is truly rooted in our community rather than the commercial interests of pharmaceutical companies,” says Brooks Turkel, CEO of Chestnut Hill Hospital. “The premise of the research was established because local patients inquired about alternatives to cholesterol lowering drugs and the potential undesirable side effects. Our cardiologists, motivated to provide their patients with alternatives, developed a life-style modification program, Change of Heart, which has served as a springboard for further research involving natural supplements. We at Chestnut Hill Hospital are very proud that the research by Drs. Becker, Gordon and their team has gained the recognition of the national medical community.”

From LATimes.com
Cheerios…the wonder drug?

That’s what the Food and Drug Administration appears to be wondering.

The FDA has sent a warning letter to General Mills, telling the company that its claims about the health benefits of eating Cheerios “would cause it to be a drug because the product is intended for use in the prevention, mitigation and treatment of disease.”

The problem: Cheerios are a food not a drug, the FDA notes in the letter, which was sent May 5 but was posted on the agency’s website today. Thus, claims that the 68-year-old whole-grain oat cereal lowers cholesterol and reduces the risk of heart disease and cancer violates federal law, the agency said.

The FDA allows some health benefits of foods to be advertised but within strict limits. For instance, a company can say that a diet low in saturated fat and high in fiber-rich foods such as fruit, vegetables and whole grains may reduce the risk of heart disease.

“The claim on your website leaves out any reference to fruits and vegetables, to fiber content and to keeping the levels of saturated fat and cholesterol in the diet low,” the agency said. “Therefore, your claim does not convey that all these factors together help to reduce the risk of heart disease and does not enable the public to understand the significance of the claim in the context of the total daily diet.”

The FDA was particularly unhappy about assertions on Cheerios boxes and its website that eating the cereal can “lower your cholesterol 4% in 6 weeks.” The FDA counters that the cereal must be approved as a drug before making such specific health claims.

General Mills spokesman Tom Forsythe said the cholesterol-lowering claim has been featured on the Cheerios box for more than two years and that the heart health claim was approved by the FDA 12 years ago. On April 20, General Mills announced results of a clinical study that showed eating two daily servings of Cheerios (1 1/2 cups each) can reduce cholesterol 10% in just a month.

“The science is not in question,” he said. “The scientific body of evidence supporting the heart health claim was the basis for FDA’s approval of the heart health claim, and the clinical study supporting Cheerios’ cholesterol-lowering benefits is very strong.”

Forsythe said the company looks forward “to discussing this with the FDA and to reaching a resolution.” General Mills faces seizure of products or an injunction against making and distributing Cheerios.

From nytimes.com

When the Food and Drug Administration approved a new type of cholesterol-lowering medicine in 2002, it did so on the basis of a handful of clinical trials covering a total of 3,900 patients. None of the patients took the medicine for more than 12 weeks, and the trials offered no evidence that it had reduced heart attacks or cardiovascular disease, the goal of any cholesterol drug.

The lack of evidence has not stopped doctors from heavily prescribing that drug, whether in a stand-alone form sold as Zetia or as a combination medicine called Vytorin. Aided by extensive consumer advertising, sales of the medicines reached $5.2 billion last year, making them among the best-selling drugs in the world. More than three million people worldwide take either drug every day.

But there is still no proof that the drugs help patients live longer or avoid heart attacks. This year Vytorin has failed two clinical trials meant to show its benefits. Worse, scientists are debating whether there is a link between the drugs and cancer.

Researchers reported last month that patients in three clinical trials had a 40 percent higher chance of dying from cancer if they took Vytorin instead of a sugar pill or another medicine, although the leader of that study says the finding might be due to chance.

Now some prominent cardiologists say that the evidence has swung so decisively against the drugs that they should not be sold. “The only place people should be taking it is in a clinical trial,” Dr. Allen J. Taylor of the Walter Reed Army Medical Center said of Zetia. (Vytorin is a single pill that combines Zetia with a statin, an older form of cholesterol-lowering medicine whose effectiveness and safety are not in question.)

On Tuesday, in a sign of the high level of interest among doctors that Vytorin and Zetia have generated, the New England Journal of Medicine will publish online two articles and an editorial about the trials that raised the potential cancer concerns.

Merck and Schering-Plough, which jointly make Vytorin and Zetia, strongly defend their medicines. The companies say that ezetimibe, the generic name for Zetia, showed no cancer risk in animal trials and argue that the cancer finding is probably a result of chance. Some independent scientists agree with the companies, saying that they are dubious of a link to cancer and that ezetimibe is a valuable treatment no matter which brand it is sold under.

About the only point on which both sides agree is that no one can judge ezetimibe’s safety and benefits for certain without more data, ideally from a clinical trial covering more than 10,000 patients and lasting several years, long enough to show that the drug actually helps patients live longer or avoid heart attacks.

But patients and doctors will have to wait years more for those results. Merck and Schering did not begin such a trial until October 2005, three years after ezetimibe was approved. And the completion date for the trial has been repeatedly postponed. Now the companies estimate that it will not be finished until at least 2012. By then tens of millions of people will have taken ezetimibe.

“I don’t think the answer on Zetia is in,” said Dr. Robert J. Temple, director for the office of medical policy at the Center for Drug Evaluation and Research, which is part of the F.D.A.

The lack of data about ezetimibe highlights an aspect of the drug approval system that even sophisticated patients may not understand. Many medicines are approved on the basis of what scientists call surrogate endpoints, like proof that they lower cholesterol, rather than because they have been shown to reduce the risk of death or disease.

For example, a cancer drug might be approved because it causes tumors to shrink, not because its manufacturer can prove that patients live longer after taking it.

Using these measures makes sense in certain circumstances, researchers say. If no treatments exist for a disease, the F.D.A. may approve a drug based on its promise in short-term trials and hope that the medicine succeeds later in larger trials where its potential to reduce death and disease will be examined directly.

But several drugs approved this way have recently proved ineffective or even dangerous. In 1999, for example, the F.D.A. approved the diabetes drug Avandia on the basis that it reduced blood sugar. Sales of Avandia and two related medicines reached $3 billion in 2006. But in 2007, an analysis of 44 clinical trials of Avandia showed that it could increase heart attacks. Since then, prescriptions for Avandia have plunged, although the drug remains on the market.

Ezetimibe is in a similar situation. The medicine has been proved to lower patients’ LDL, or bad, cholesterol by 15 to 20 percent. Decades of research links lower cholesterol to a reduced risk of heart attacks. And cholesterol-lowering drugs called statins, including Lipitor and Crestor, have been proved to reduce heart attacks. But statins work very differently than ezetimibe, and no one has proved that ezetimibe offers the same benefits as statins.

“The F.D.A. set the bar too low on the initial approval,” said Dr. Steven Nissen, chairman of cardiology at the Cleveland Clinic. “It would have been a lot better if the agency had said, ‘Show us that you do more than lower LDL a little bit, show us evidence of effectiveness.’ ”

Further, when the F.D.A. approved Zetia, several statins were already on the market, giving patients other options to lower their cholesterol. So the agency’s decision to approve Zetia without requiring larger trials is especially puzzling, Dr. Nissen said.

Dr. Temple said the link between LDL cholesterol and heart disease was so strong that the agency was comfortable approving drugs on the basis that they lowered cholesterol alone. “We accept LDL cholesterol as a valid surrogate,” he said.

But the failure nearly two years ago of torcetrapib, an experimental drug from Pfizer, spotlighted the risks of using drugs without long-term data. Torcetrapib raised HDL cholesterol — the so-called “good” cholesterol, which is known to reduce the risk of heart problems.

But the F.D.A. chose not to approve torcetrapib on the basis of its effects on HDL. Instead, the agency required that Pfizer first conduct a large trial. In December 2006, the trial revealed that torcetrapib raised patients’ risk of death by 60 percent, forcing Pfizer to discontinue development of the drug.

Dr. Curt D. Furberg, an epidemiologist and drug safety expert at Wake Forest University, said that before approving drugs the F.D.A. should require that drug companies conduct large trials on whether they reduce death and disease, except in rare cases where no alternatives exist. If the agency approves drugs without such data, that fact should be noted prominently on a drug’s label, Dr. Furberg said.

Pharmaceutical companies argue against changing the current approval system. Determining whether a drug reduces death or disease can require a trial that enrolls 10,000 or more patients and lasts four years or more. Requiring longer and costlier trials might discourage the development of new medicines, said Ken Johnson, senior vice president of the Pharmaceutical Research and Manufacturers of America.

He said the current system enabled patients “to access life-saving and life-enhancing remedies more quickly.”

The F.D.A. does seem to be taking a harder line on new diabetes and heart medicines. In April, the agency turned down an HDL-cholesterol-raising drug from Merck that did not have long-term trial data. And in July, an F.D.A. advisory panel recommended 14-2 that companies conduct long-term trials on new diabetes medicines.

But for drugs already on the market, no such requirement exists. So ezetimibe remains heavily prescribed despite questions about both its effectiveness and whether it is linked to cancer.

In January, Merck and Schering announced that Vytorin — the combination of ezetimibe and a generic statin called simvastatin — had failed a clinical trial meant to show that it could slow the growth of arterial plaque that could cause heart attacks.

Then, in July, Norwegian researchers reported that another trial showed that patients taking Vytorin died from cancer more often than those taking a placebo, or sugar pill. In two other clinical trials still going on, patients taking Vytorin have also been more likely to die from cancer than those not taking it. In all, 136 of about 11,000 people taking Vytorin in the three trials have died of various kinds of cancer, compared with 95 out of 11,000 who took placebo or simvastatin alone.

With little long-term data about ezetimibe’s risks, scientists are scrambling to find an explanation for the seeming cancer link. Some oncologists agree with Merck and Schering that the cancer findings are probably due to chance.

But other scientists say they have a plausible explanation for why ezetimibe may cause cancer. Ezetimibe works by blocking the intestine from absorbing cholesterol. But it also blocks the absorption of closely related compounds called plant sterols, which are found in nuts and vegetables. Some studies have shown that people who eat large amounts of plant sterols have lower cancer rates than those who do not.

Dr. Peter G. Bradford, a pharmacologist at the University of Buffalo who has extensively studied plant sterols, said that in laboratory tests, sterols promote cell death in a way that could make them valuable anti-cancer agents as weapons against tumors. By blocking sterol absorption, ezetimibe could be promoting cancer , he said.

“One might envision that link,” he said. “This is a very large question.”

Merck and Schering noted that the drug showed no carcinogenic effects in mice. In addition, the link between sterols and cancer remains hypothetical and has never been proved in a clinical trial. Further, cancer typically takes many years to develop in humans, so the theory that ezetimibe could cause cancer in a year or two is not plausible, they say.

Some leading cancer researchers agree. Dr. Tyler Jacks, director of the Koch Institute at the Massachusetts Institute of Technology, said Merck had asked him to examine the results of the Norwegian trial and he concluded it was probably a false signal. If ezetimibe causes cancer, its effects should have become more pronounced as the trial went on, Dr. Jacks said. Instead, the gap between patients who took Vytorin and those who took a placebo did not widen over the length of the trial, he said.

Dr. Terje Pedersen, the Norwegian cardiologist who conducted the trial, said he also doubted that Vytorin caused the excess of cancers seen in the study. Even very dangerous carcinogens — like cigarettes and radiation — typically require several years, even decades, to cause cancer. Given that fact, ezetimibe would have to be extraordinarily and implausibly carcinogenic to have noticeable effects in a three-year trial, he said.

“The duration of the trial is not long enough to believe that the treatment would cause cancer,” Dr. Pedersen said.

Still, the concerns about ezetimibe’s potential risks and lack of effectiveness have discouraged some patients from using the medicine. In the United States, prescriptions for Vytorin and Zetia have fallen 40 percent this year.

Dr. Jacks said Merck and Schering could not easily resolve the questions about ezetimibe’s potential risks. “The answer is to get more data,” he said.